APL Bioengineering最新文献

{"title":"Hemodynamics of thrombus formation in intracranial aneurysms: An <i>in silico</i> observational study.","authors":"Qiongyao Liu,&nbsp;Ali Sarrami-Foroushani,&nbsp;Yongxing Wang,&nbsp;Michael MacRaild,&nbsp;Christopher Kelly,&nbsp;Fengming Lin,&nbsp;Yan Xia,&nbsp;Shuang Song,&nbsp;Nishant Ravikumar,&nbsp;Tufail Patankar,&nbsp;Zeike A Taylor,&nbsp;Toni Lassila,&nbsp;Alejandro F Frangi","doi":"10.1063/5.0144848","DOIUrl":"https://doi.org/10.1063/5.0144848","url":null,"abstract":"<p><p>How prevalent is spontaneous thrombosis in a population containing all sizes of intracranial aneurysms? How can we calibrate computational models of thrombosis based on published data? How does spontaneous thrombosis differ in normo- and hypertensive subjects? We address the first question through a thorough analysis of published datasets that provide spontaneous thrombosis rates across different aneurysm characteristics. This analysis provides data for a subgroup of the general population of aneurysms, namely, those of large and giant size (>10 mm). Based on these observed spontaneous thrombosis rates, our computational modeling platform enables the first <i>in silico</i> observational study of spontaneous thrombosis prevalence across a broader set of aneurysm phenotypes. We generate 109 virtual patients and use a novel approach to calibrate two trigger thresholds: residence time and shear rate, thus addressing the second question. We then address the third question by utilizing this calibrated model to provide new insight into the effects of hypertension on spontaneous thrombosis. We demonstrate how a mechanistic thrombosis model calibrated on an intracranial aneurysm cohort can help estimate spontaneous thrombosis prevalence in a broader aneurysm population. This study is enabled through a fully automatic multi-scale modeling pipeline. We use the clinical spontaneous thrombosis data as an indirect population-level validation of a complex computational modeling framework. Furthermore, our framework allows exploration of the influence of hypertension in spontaneous thrombosis. This lays the foundation for <i>in silico</i> clinical trials of cerebrovascular devices in high-risk populations, e.g., assessing the performance of flow diverters in aneurysms for hypertensive patients.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"7 3","pages":"036102"},"PeriodicalIF":6.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10329514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9814114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surface electromyography using dry polymeric electrodes.","authors":"Nicolas Steenbergen,&nbsp;Ivan Busha,&nbsp;Alexis Morgan,&nbsp;Collin Mattathil,&nbsp;Arieh Levy Pinto,&nbsp;Fotios Spyridakos,&nbsp;Ivan Sokolovskiy,&nbsp;Bogachan Tahirbegi,&nbsp;Christopher Chapman,&nbsp;Estelle Cuttaz,&nbsp;Karina Litvinova,&nbsp;Josef Goding,&nbsp;Rylie Green","doi":"10.1063/5.0148101","DOIUrl":"https://doi.org/10.1063/5.0148101","url":null,"abstract":"<p><p>Conventional wet Ag/AgCl electrodes are widely used in electrocardiography, electromyography (EMG), and electroencephalography (EEG) and are considered the gold standard for biopotential measurements. However, these electrodes require substantial skin preparation, are single use, and cannot be used for continuous monitoring (>24 h). For these reasons, dry electrodes are preferable during surface electromyography (sEMG) due to their convenience, durability, and longevity. Dry conductive elastomers (CEs) combine conductivity, flexibility, and stretchability. In this study, CEs combining poly(3,4-ehtylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) in polyurethane are explored as dry, skin contacting EMG electrodes. This study compares these CE electrodes to commercial wet Ag/AgCl electrodes in five subjects, classifying four movements: open hand, fist, wrist extension, and wrist flexion. Classification accuracy is tested using a backpropagation artificial neural network. The control Ag/AgCl electrodes have a 98.7% classification accuracy, while the dry conductive elastomer electrodes have a classification accuracy of 99.5%. As a conclusion, PEDOT based dry CEs were shown to successfully function as on-skin electrodes for EMG recording, matching the performance of Ag/AgCl electrodes, while addressing the need for minimal skin prep, no gel, and wearable technology.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"7 3","pages":"036115"},"PeriodicalIF":6.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10497318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10316244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oscillatory shear stress-induced downregulation of TET1s injures vascular endothelial planar cell polarity by suppression of actin polymerization.","authors":"Kai Qu,&nbsp;Caihong Wang,&nbsp;Lu Huang,&nbsp;Xian Qin,&nbsp;Kun Zhang,&nbsp;Juhui Qiu,&nbsp;Guixue Wang","doi":"10.1063/5.0141289","DOIUrl":"https://doi.org/10.1063/5.0141289","url":null,"abstract":"<p><p>Vascular endothelial polarity induced by blood flow plays crucial roles in the development of atherosclerosis. Loss of endothelial polarity leads to an increase in permeability and leukocyte recruitment, which are crucial hallmarks of atherosclerotic initiation. Endothelial cells exhibit a morphological adaptation to hemodynamic shear stress and possesses planar cell polarity to the direction of blood flow. However, the mechanism of how hemodynamic shear stress regulates endothelial planar cell polarity has not been firmly established. Here, we found that TET1s, a short isoform of Tet methylcytosine dioxygenase 1, was a mediator in the regulation of the planar cell polarity in endothelial cells in response to hemodynamic shear stress. In the process, low expression of TET1s induced by oscillatory shear stress led to the endothelial planar polarity damage through inhibition of F-actin polymerization. TET1s can regulate demethylation level of the sFRP-1 promoter to alter the expression of sFRP-1, which affects the interaction of sFRP-1/Fzd4 and F-actin polymerization. Our study revealed the mechanism of how TET1s mediates endothelial planar cell polarity in response to hemodynamic shear stress and provides a new insight for the prevention of atherosclerosis.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"7 3","pages":"036104"},"PeriodicalIF":6.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10393427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9932988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging trends in the development of flexible optrode arrays for electrophysiology.","authors":"Reem M Almasri,&nbsp;François Ladouceur,&nbsp;Damia Mawad,&nbsp;Dorna Esrafilzadeh,&nbsp;Josiah Firth,&nbsp;Torsten Lehmann,&nbsp;Laura A Poole-Warren,&nbsp;Nigel H Lovell,&nbsp;Amr Al Abed","doi":"10.1063/5.0153753","DOIUrl":"https://doi.org/10.1063/5.0153753","url":null,"abstract":"<p><p>Optical-electrode (optrode) arrays use light to modulate excitable biological tissues and/or transduce bioelectrical signals into the optical domain. Light offers several advantages over electrical wiring, including the ability to encode multiple data channels within a single beam. This approach is at the forefront of innovation aimed at increasing spatial resolution and channel count in multichannel electrophysiology systems. This review presents an overview of devices and material systems that utilize light for electrophysiology recording and stimulation. The work focuses on the current and emerging methods and their applications, and provides a detailed discussion of the design and fabrication of flexible arrayed devices. Optrode arrays feature components non-existent in conventional multi-electrode arrays, such as waveguides, optical circuitry, light-emitting diodes, and optoelectronic and light-sensitive functional materials, packaged in planar, penetrating, or endoscopic forms. Often these are combined with dielectric and conductive structures and, less frequently, with multi-functional sensors. While creating flexible optrode arrays is feasible and necessary to minimize tissue-device mechanical mismatch, key factors must be considered for regulatory approval and clinical use. These include the biocompatibility of optical and photonic components. Additionally, material selection should match the operating wavelength of the specific electrophysiology application, minimizing light scattering and optical losses under physiologically induced stresses and strains. Flexible and soft variants of traditionally rigid photonic circuitry for passive optical multiplexing should be developed to advance the field. We evaluate fabrication techniques against these requirements. We foresee a future whereby established telecommunications techniques are engineered into flexible optrode arrays to enable unprecedented large-scale high-resolution electrophysiology systems.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"7 3","pages":"031503"},"PeriodicalIF":6.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10222485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D photopolymerized microstructured scaffolds influence nuclear deformation, nucleo/cytoskeletal protein organization, and gene regulation in mesenchymal stem cells.","authors":"Francesca Donnaloja,&nbsp;Manuela Teresa Raimondi,&nbsp;Letizia Messa,&nbsp;Bianca Barzaghini,&nbsp;Federica Carnevali,&nbsp;Emanuele Colombo,&nbsp;Davide Mazza,&nbsp;Chiara Martinelli,&nbsp;Lucia Boeri,&nbsp;Federica Rey,&nbsp;Cristina Cereda,&nbsp;Roberto Osellame,&nbsp;Giulio Cerullo,&nbsp;Stephana Carelli,&nbsp;Monica Soncini,&nbsp;Emanuela Jacchetti","doi":"10.1063/5.0153215","DOIUrl":"https://doi.org/10.1063/5.0153215","url":null,"abstract":"<p><p>Mechanical stimuli from the extracellular environment affect cell morphology and functionality. Recently, we reported that mesenchymal stem cells (MSCs) grown in a custom-made 3D microscaffold, the Nichoid, are able to express higher levels of stemness markers. In fact, the Nichoid is an interesting device for autologous MSC expansion in clinical translation and would appear to regulate gene activity by altering intracellular force transmission. To corroborate this hypothesis, we investigated mechanotransduction-related nuclear mechanisms, and we also treated spread cells with a drug that destroys the actin cytoskeleton. We observed a roundish nuclear shape in MSCs cultured in the Nichoid and correlated the nuclear curvature with the import of transcription factors. We observed a more homogeneous euchromatin distribution in cells cultured in the Nichoid with respect to the Flat sample, corresponding to a standard glass coverslip. These results suggest a different gene regulation, which we confirmed by an RNA-seq analysis that revealed the dysregulation of 1843 genes. We also observed a low structured lamina mesh, which, according to the implemented molecular dynamic simulations, indicates reduced damping activity, thus supporting the hypothesis of low intracellular force transmission. Also, our investigations regarding lamin expression and spatial organization support the hypothesis that the gene dysregulation induced by the Nichoid is mainly related to a reduction in force transmission. In conclusion, our findings revealing the Nichoid's effects on MSC behavior is a step forward in the control of stem cells via mechanical manipulation, thus paving the way to new strategies for MSC translation to clinical applications.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"7 3","pages":"036112"},"PeriodicalIF":6.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10276011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gelatin-modified 3D printed PGS elastic hierarchical porous scaffold for cartilage regeneration.","authors":"Sinan Wang,&nbsp;Hongying Chen,&nbsp;Jinyi Huang,&nbsp;Sisi Shen,&nbsp;Zhengya Tang,&nbsp;Xiaoyan Tan,&nbsp;Dong Lei,&nbsp;Guangdong Zhou","doi":"10.1063/5.0152151","DOIUrl":"https://doi.org/10.1063/5.0152151","url":null,"abstract":"<p><p>Regenerative cartilage replacements are increasingly required in clinical settings for various defect repairs, including bronchial cartilage deficiency, articular cartilage injury, and microtia reconstruction. Poly (glycerol sebacate) (PGS) is a widely used bioelastomer that has been developed for various regenerative medicine applications because of its excellent elasticity, biodegradability, and biocompatibility. However, because of inadequate active groups, strong hydrophobicity, and limited ink extrusion accuracy, 3D printed PGS scaffolds may cause insufficient bioactivity, inefficient cell inoculation, and inconsistent cellular composition, which seriously hinders its further cartilage regenerative application. Here, we combined 3D printed PGS frameworks with an encapsulated gelatin hydrogel to fabricate a PGS@Gel composite scaffold. PGS@Gel scaffolds have a controllable porous microstructure, with suitable pore sizes and enhanced hydrophilia, which could significantly promote the cells' penetration and adhesion for efficient chondrocyte inoculation. Furthermore, the outstanding elasticity and fatigue durability of the PGS framework enabled the regenerated cartilage built by the PGS@Gel scaffolds to resist the dynamic <i>in vivo</i> environment and maintain its original morphology. Importantly, PGS@Gel scaffolds increased the rate of cartilage regeneration concurrent with scaffold degradation. The scaffold was gradually degraded and integrated to form uniform, dense, and mature regenerated cartilage tissue with little scaffold residue.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"7 3","pages":"036105"},"PeriodicalIF":6.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10404141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9944796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"User-friendly microfluidic system reveals native-like morphological and transcriptomic phenotypes induced by shear stress in proximal tubule epithelium.","authors":"Natalie N Khalil,&nbsp;Andrew P Petersen,&nbsp;Cheng J Song,&nbsp;Yibu Chen,&nbsp;Kaelyn Takamoto,&nbsp;Austin C Kellogg,&nbsp;Elaine Zhelan Chen,&nbsp;Andrew P McMahon,&nbsp;Megan L McCain","doi":"10.1063/5.0143614","DOIUrl":"https://doi.org/10.1063/5.0143614","url":null,"abstract":"<p><p>Drug-induced nephrotoxicity is a leading cause of drug attrition, partly due to the limited relevance of pre-clinical models of the proximal tubule. Culturing proximal tubule epithelial cells (PTECs) under fluid flow to mimic physiological shear stress has been shown to improve select phenotypes, but existing flow systems are expensive and difficult to implement by non-experts in microfluidics. Here, we designed and fabricated an accessible and modular flow system for culturing PTECs under physiological shear stress, which induced native-like cuboidal morphology, downregulated pathways associated with hypoxia, stress, and injury, and upregulated xenobiotic metabolism pathways. We also compared the expression profiles of shear-dependent genes in our <i>in vitro</i> PTEC tissues to that of <i>ex vivo</i> proximal tubules and observed stronger clustering between <i>ex vivo</i> proximal tubules and PTECs under physiological shear stress relative to PTECs under negligible shear stress. Together, these data illustrate the utility of our user-friendly flow system and highlight the role of shear stress in promoting native-like morphological and transcriptomic phenotypes in PTECs <i>in vitro</i>, which is critical for developing more relevant pre-clinical models of the proximal tubule for drug screening or disease modeling.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"7 3","pages":"036106"},"PeriodicalIF":6.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10424157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10121639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A sense of proximity: Cell packing modulates oxygen consumption.","authors":"Ermes Botte,&nbsp;Piera Mancini,&nbsp;Chiara Magliaro,&nbsp;Arti Ahluwalia","doi":"10.1063/5.0160422","DOIUrl":"https://doi.org/10.1063/5.0160422","url":null,"abstract":"<p><p>Accurately modeling oxygen transport and consumption is crucial to predict metabolic dynamics in cell cultures and optimize the design of tissue and organ models. We present a methodology to characterize the Michaelis-Menten oxygen consumption parameters <i>in vitro</i>, integrating novel experimental techniques and computational tools. The parameters were derived for hepatic cell cultures with different dimensionality (i.e., 2D and 3D) and with different surface and volumetric densities. To quantify cell packing regardless of the dimensionality of cultures, we devised an image-based metric, referred to as the proximity index. The Michaelis-Menten parameters were related to the proximity index through an uptake coefficient, analogous to a diffusion constant, enabling the quantitative analysis of oxygen dynamics across dimensions. Our results show that Michaelis-Menten parameters are not constant for a given cell type but change with dimensionality and cell density. The maximum consumption rate per cell decreases significantly with cell surface and volumetric density, while the Michaelis-Menten constant tends to increase. In addition, the dependency of the uptake coefficient on the proximity index suggests that the oxygen consumption rate of hepatic cells is superadaptive, as they modulate their oxygen utilization according to its local availability and to the proximity of other cells. We describe, for the first time, how cells consume oxygen as a function of cell proximity, through a quantitative index, which combines cell density and dimensionality. This study enhances our understanding of how cell-cell interaction affects oxygen dynamics and enables better prediction of aerobic metabolism in tissue models, improving their translational value.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"7 3","pages":"036111"},"PeriodicalIF":6.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10468216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10152943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluid shear stress enhances natural killer cell's cytotoxicity toward circulating tumor cells through NKG2D-mediated mechanosensing.","authors":"Bing Hu,&nbsp;Ying Xin,&nbsp;Guanshuo Hu,&nbsp;Keming Li,&nbsp;Youhua Tan","doi":"10.1063/5.0156628","DOIUrl":"https://doi.org/10.1063/5.0156628","url":null,"abstract":"<p><p>Tumor cells metastasize to distant organs mainly via hematogenous dissemination, in which circulating tumor cells (CTCs) are relatively vulnerable, and eliminating these cells has great potential to prevent metastasis. In vasculature, natural killer (NK) cells are the major effector lymphocytes for efficient killing of CTCs under fluid shear stress (FSS), which is an important mechanical cue in tumor metastasis. However, the influence of FSS on the cytotoxicity of NK cells against CTCs remains elusive. We report that the death rate of CTCs under both NK cells and FSS is much higher than the combined death induced by either NK cells or FSS, suggesting that FSS may enhance NK cell's cytotoxicity. This death increment is elicited by shear-induced NK activation and granzyme B entry into target cells rather than the death ligand TRAIL or secreted cytokines TNF-α and IFN-γ. When NK cells form conjugates with CTCs or adhere to MICA-coated substrates, NK cell activating receptor NKG2D can directly sense FSS to induce NK activation and degranulation. These findings reveal the promotive effect of FSS on NK cell's cytotoxicity toward CTCs, thus providing new insight into immune surveillance of CTCs within circulation.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"7 3","pages":"036108"},"PeriodicalIF":6.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10423075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10371404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A low-profile electromechanical packaging system for soft-to-flexible bioelectronic interfaces.","authors":"Florian Fallegger,&nbsp;Alix Trouillet,&nbsp;Florent-Valéry Coen,&nbsp;Giuseppe Schiavone,&nbsp;Stéphanie P Lacour","doi":"10.1063/5.0152509","DOIUrl":"https://doi.org/10.1063/5.0152509","url":null,"abstract":"<p><p>Interfacing the human body with the next generation of electronics requires technological advancement in designing and producing bioelectronic circuits. These circuits must integrate electrical functionality while simultaneously addressing limitations in mechanical compliance and dynamics, biocompatibility, and consistent, scalable manufacturing. The combination of mechanically disparate materials ranging from elastomers to inorganic crystalline semiconductors calls for modular designs with reliable and scalable electromechanical connectors. Here, we report on a novel interconnection solution for soft-to-flexible bioelectronic interfaces using a patterned and machined flexible printed circuit board, which we term FlexComb, interfaced with soft transducing systems. Using a simple assembly process, arrays of protruding \"fingers\" bearing individual electrical terminals are laser-machined on a standard flexible printed circuit board to create a comb-like structure, namely, the FlexComb. A matching pattern is also machined in the soft system to host and interlock electromechanically the FlexComb connections via a soft electrically conducting composite. We examine the electrical and electromechanical properties of the interconnection and demonstrate the versatility and scalability of the method through various customized submillimetric designs. In a pilot <i>in vivo</i> study, we validate the stability and compatibility of the FlexComb technology in a subdural electrocorticography system implanted for 6 months on the auditory cortex of a minipig. The FlexComb provides a reliable and simple technique to bond and connect soft transducing systems with flexible or rigid electronic boards, which should find many implementations in soft robotics and wearable and implantable bioelectronics.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"7 3","pages":"036109"},"PeriodicalIF":6.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10439817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10490390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}